The broad objective of this application is to identify neural mechanisms that cause migraineurs to seek sanctuary in the dark during attacks in effort to escape what they describe as my head hurts more and I feel worse when I am exposed to light. The long-term objectives are to identify the impact of light on sensory, affective and autonomic neurological functions during migraine (human study), and discover the neural pathways through which lights alter these functions (animal study). Leading up to this grant proposal are years of listening to patients' testimonies which taught us that exposure to different kind of lights can trigger different symptoms in migraineurs with normal eyesight as compared to blind and color-blind migraineurs. Based on what we heard, we postulated that exacerbation of headache by light is one of many reasons why migraineus seek the dark during migraine and that different colors of lights have the capacity to trigger different neurological symptoms. Mechanistically, we hypothesized that during migraine, activity of neurons in brain regions that mediate different aspects of sensory, emotional, and autonomic responses to pain is modulated by both headache and light through signals transmitted to them from the spinal trigeminal nucleus and the optic nerve. In the clinical study, we will determine the effects of different colos of light on the intensity of migraine headache and its many associated symptoms. Two groups of migraineurs (normal eyesight and visually-impaired) and a control group will be expose to different intensities of white, blue, green, yellow and red lights (delivered through an FDA-approved photic stimulator) when they are pain-free and during an attack. Data analysis and interpretation will include strength of electroretinography and visual evoked potential signals (waveforms) as well as documentation of sensory, affective and physiological changes. In the animal study, we will determine whether neurons that play a role in the neurological symptoms that are altered by light in patients receive direct input from the retina and brain areas involved in the transmission of migraine headache. These studies will combine psychophysical observations in human subjects with tract-tracing, immunohistochemical, molecular and physiological techniques in animals.